Management of Acromioclavicular Joint Disease by Manual Therapy Versus Corticosteroid Injections: the Protocol of a Non-­Inferiority Study

Open access Protocol BMJ Open: first published as 10.1136/bmjopen-2019-034439 on 10 December 2020. Downloaded from Management of acromioclavicular joint disease by manual therapy versus corticosteroid injections: the protocol of a non-­inferiority study

Alexia Michaut,1 Lucie Planche,2 Lucie Auzanneau,2 Grégoire Cormier ‍ ‍ 2

To cite: Michaut A, ABSTRACT Strengths and limitations of this study Planche L, Auzanneau L, Introduction Degenerative acromioclavicular joint pain et al. Management of accounts for about 4% of shoulder pain. Various medical acromioclavicular joint disease ►► This study is a randomised and controlled study. and non-medical­ treatment strategies are available for by manual therapy versus ►► It is the first study comparing corticosteroid injec- acromioclavicular joint disease but it is difficult to conduct corticosteroid injections: tions and joint manual therapy for acromioclavicular the protocol of a non-­ a comparative evaluation of these treatments. The few joint disease. studies dealing with the medical management of the inferiority study. BMJ Open ►► Manual therapy is a topic regularly mentioned by 2020;10:e034439. doi:10.1136/ disease have conducted no comparative assessment of patients and little known by physicians. bmjopen-2019-034439 drug therapies, physiotherapy, joint manipulation and ►► The non-blinded­ patient and the monocentric aspect corticosteroid injections. The primary goal of this study ►► Prepublication history and are limitations of the study design. additional material for this is to determine whether manual therapy is not inferior to paper are available online. To ultrasound-guided­ injection of a corticosteroid preparation view these files, please visit to decrease acromiocalvicular joint pain at 3 months. Shoulder pain is a widespread complaint in the journal online (http://​dx.​doi.​ Methods and analysis The acromioclavicular org/10.​ ​1136/bmjopen-​ ​2019-​ the general population, with an annual prev- arthropathy managed by manual therapy is a monocentric, 2 034439). comparative, randomised, controlled, non-­inferiority alence ranging from 5% to 47%. Acromio- study conducted in the Rheumatology Department of clavicular (AC) joint pain accounts for about Received 19 September 2019 Vendée Departmental Hospital, involving two parallel 4% of shoulder pains and can be identified Revised 17 July 2020 2 Accepted 20 July 2020 groups receiving either corticosteroid injections or manual on clinical examination. Degenerative AC

therapy. The inclusion criteria are patients who suffer from joint disease occurs most commonly after the http://bmjopen.bmj.com/ pain in the shoulder or the proximal part of the arm, with age of 50 years and is more frequent in men pain located on palpation of the acromioclavicular joint in this age group.3 Diagnosis is made on the associated with a positive cross-­arm test and a positive basis of history taking and clinical examina- O’Brien test. Randomisation will be at a 1:1 ratio. The tion with specific tests such as the cross-­arm injection group will receive a single ultrasound-guided­ test. It is positive if by a cross adduction and injection of 1 mL of Diprostène and the manual therapy horizontal adduction with hand to the top group will receive between one and three sessions at of the opposite shoulder the pain is located intervals of one per week. The primary outcome will be to compare the Visual Analogue Scale for pain-­activity-rela­ ted to the AC joint. The O’Brien test is specific, on September 23, 2021 by guest. Protected copyright. score at 3 months for both groups. if the pain is located in the AC joint during Ethics and dissemination The study project has been anterior flexion, adduction and maximal 4 approved by the appropriate ethics committee (Committee internal rotation against resistance. An X-ray­ for the Protection of Patients Ouest II in Angers, 30 of the centre of the AC joint should then be © Author(s) (or their employer(s)) 2020. Re-­use April 2019, with the registration number of 2019/22). taken to confirm degenerative joint disease. 5 permitted under CC BY-­NC. No In agreement with current French regulations, signed In their literature review, Chaudhury report commercial re-­use. See rights informed written consent will be obtained from each that it is difficult to conduct a comparative and permissions. Published by patient. Results of the main trial and of the secondary evaluation of the various medical and non-­ BMJ. endpoints will be submitted for publication in a peer-­ medical treatment strategies for AC joint pain 1Department of Rheumatology, reviewed journal. because these strategies cannot be compared Departmental Hospital Center, La Trial registration number NCT03951480. Roche sur Yon, Vendée, France in a blinded fashion. The few studies dealing 2Departmental of Rheumatology, with the medical management of the disease Vendée Departmental Hospital conducted no comparative assessment of Center, La Roche sur Yon, France INTRODUCTION drug therapies, physiotherapy, joint manipu- 5 Correspondence to This paper was written in accordance with the lation or corticosteroid injections. Dr Alexia Michaut; Standard Protocol Items: Recommendations The Visual Analogue Scale (VAS) to measure alexia.​ ​michaut@chd-​ ​vendee.fr​ for Interventional Trials guidelines.1 pain at rest, pressure pain and night-time­

Michaut A, et al. BMJ Open 2020;10:e034439. doi:10.1136/bmjopen-2019-034439 1 Open access BMJ Open: first published as 10.1136/bmjopen-2019-034439 on 10 December 2020. Downloaded from pain is often used.6 7 Pain VAS is the most commonly of symptoms was shorter and therapeutic failure was far used method to rate a patient’s subjective assessment of less often reported after corticosteroid injections than pain. It has good reproducibility, is able to track pain it was after manipulation or physiotherapy. In this study, progression in the same patient and is easy to use even the cause of the pain was not taken into consideration, in patients with cognitive impairment.8 In one study of with the authors only indicating the presence (or lack) of Sabeti-­Aschraf6 after a treatment by one infiltration, the synovitis. It seems reasonable to propose manipulation in VAS pressure pain score progressed from 7.8±1.99 at T0 the management of cases of shoulder pain without syno- to 5.9±3.41 at T2 after 2 weeks of treatment (p<0.0013), vial involvement, as in AC osteoarthritis. while the pain at rest score went from 6.9±1.57 at T0 to In the literature review of Peek17 the cited randomised 5.8±2.25 at T2 (p<0.0213). In a second study of Sabeti-­ controlled trials analysed thoracic manual therapies in 7 Aschraf the VAS pressure pain score progressed from comparison to conventional treatments such as anal- 5.76±2.00 to 2.68±2.34 while the night-time­ score went gesics, non-steroid­ anti-inflammator­ y drugs (NSAIDs), from 5.22±2.27 to 2.42±2.31 after 3 weeks of treatment, corticosteroid injections.15 determined the short-term­ irrespective of the mode of injection (p<0.0001). and long-­term effects of manual therapy management of There are several shoulder function tests, including the patients with non-acute­ AC joint pain. After six sessions 9 Constant Score, which was used in the studies referred of manual therapy, significant short-­term and long-term­ to above but which has not been validated in a French improvement in pain and disability was observed. Assess- version. It is difficult to perform in daily practice, as it ments were made on the basis of Shoulder Pain and involves the measurement of angles of joint amplitudes Disability Index scores and the American Shoulder and that are of interest to surgeons but that are not useful Elbow Surgeon Scale. The pain VAS was not used. All these for our study. The Disabilities of the Arm, Shoulder and studies point towards some beneficial effects of manual 10 Hand (DASH) questionnaire is specifically used to therapy for the management of pain and disability in the assess the functional disability of patients during leisure shoulder. However, they involved small patient sample activities and in the workplace. The test is widely used in sizes, gave no details about the initial shoulder complaint medical studies, in particular for shoulder injections for and did not compare the effects of manual therapy and pain management. The questionnaire is easy to perform, injections. does not require any joint measurements and has been validated in a French-language­ version. The Oxford Objectives Shoulder Score is another patient-based­ questionnaire, Main objective which is significantly correlated with the Constant Score Comparing the medium-­term efficacy of manual therapy but is easier to implement.11 The results help guide the management of pain in degenerative AC joint disease choice of either medical or surgical management. This with that of ultrasound-guided­ injection of a corticoid evaluation, however, falls outside the scope of our study. http://bmjopen.bmj.com/ preparation (Diprostene) is the main objective. The Specific AC Score, a new assessment tool validated in English by surgeons, is too recent to have been compared with other methods.12 Secondary objectives Regarding ultrasound-guided­ injections, in the study of ►► Progression of pain at rest and of night-time­ and Park13 patients with shoulder pain had a better functional activity-­related pain over the 7 days before visits at day outcome after 3 months and 6 months with ultrasound-­ 0 (D0), month 1 (M1) and month 3 (M3). Recording guided injections. The findings suggest that ultrasound-­ of the mean and greatest pain during the preceding week. guided injections are more effective. on September 23, 2021 by guest. Protected copyright. Performed by an experienced physician, manual ther- ►► Progression of pain at rest at visits at D0, M1, and M3 apies could act as a complement to conventional medi- and of activity-­related pain at visits at D0 and M1. cine for mild joint pain such as that associated with ►► Progression of upper-­limb-­related quality of life as osteoarthritis. They could be an alternative to injections assessed by the DASH self-administered­ questionnaire because the study of Rhon reported transient pain with at D0, M1 and M3. injections.14a Harris15a Winters16 compared corticosteroid ►► Assessment of the clinical tolerance of manipulations injections with physiotherapy (in the form of massages compared with that of injections on the basis of pain and self-administered­ exercises) and with passive move- VAS scores at D0. ment and joint manipulation performed by a manual ►► Assessment of the patient’s perception of manipula- therapist for shoulder complaints. The duration of pain tions compared with that of injections at D0 on the was considerably shorter after manipulation as compared basis of replies to three questions, two before the with physiotherapy. Almost 70% of patients in the manip- session and one after: ulation group considered themselves cured compared Which procedure do you think will be more painful? with only 10% of those who had received physiotherapy Which do you think will be more effective? Would you (p<0.001). In addition, manipulation was associated with recommend the procedure that you underwent to a less therapeutic failure as compared with physiotherapy. relative or friend? In patients with synovitis of the shoulder, the duration ►► Assess the patient’s perception of disease progression.

2 Michaut A, et al. BMJ Open 2020;10:e034439. doi:10.1136/bmjopen-2019-034439 Open access BMJ Open: first published as 10.1136/bmjopen-2019-034439 on 10 December 2020. Downloaded from

►► Describe the adverse effects and events reported at ►► Pregnant or breastfeeding women. D0, M1 and M3 (booklet). ►► Patients under guardianship or curatorship or ►► Record the consumption of analgesics and NSAIDs deprived of liberty. between D0 and M3 (booklet). ►► Patients participating in another interventional clinical research study involving a drug or medical Methods device. Study design ►► Patients whom the investigator considers unable to It is a monocentric, comparative, randomised, controlled comply with the study protocol. non-­inferiority study involving two parallel groups ►► Patients with a diagnosis of associated fibromyalgia. receiving either corticosteroid injections or manual therapy. Intervention The study was conducted in the Rheumatology Depart- The inclusion and exclusion criteria will be checked during ment of the Vendée Departmental Hospital (CHD), La the enrolment visit. The aims and protocol of the study will Roche sur Yon, France. then be explained to eligible patients, who will be given oral and written information and asked to sign a consent form Inclusion criteria (cf online supplemental file). During this consultation, the ►► Patients aged between 40 and 70 years. groups will be randomised so as to schedule in advance the ►► Pain in the shoulder or the proximal part of the arm sessions for the group allocated to manual therapy. Rando- with pain located on palpation of the AC joint+posi- misation will be done through the Ennov Clinical website tive cross-­arm test+positive O’Brien test. according to a ratio of 1:1. ►► The absence of pain or <4 score on Hawkins test. Depending on the group to which they have been allo- ►► Symptomatic AC osteoarthritis confirmed by X-­ray. cated, patients will receive either a single ultrasound-guided­ ►► Pain at rest or activity-related­ pain (VAS ≥4) with a injection of 1mL of Diprostene or manual therapy manage- duration of longer than 3 months. ment comprising three sessions of 30 min each at intervals 14 ►► Patient able to understand the protocol and give of 1 week. In line with usual practice, it will be possible to informed consent. halt these sessions after assessment of clinical progress by the ►► Patient with social security coverage. therapist. If the VAS score is <2 for activity-­related pain, it will NSAIDs or oral analgesics can be taken during the be rated as not painful or mildly painful and manual therapy study period. will be discontinued. The manual therapy was performed by only one rheuma- Exclusion criteria tologist practicing in public hospital, with 5 years of manual ►► Contraindication to scapular or cervical manipulation. medicine training and having experience of 7 years of prac-

►► Contraindication to injections (unbalanced diabetes tice. It consists of performing contractions and isometric http://bmjopen.bmj.com/ with HbA1c >8.5%, unbalanced hypertension and stretchings of the shoulder and neck muscles (deltoid, current infection). scapula elevator, trapezoid, scalens, sternocleidomastoid ►► Recent trauma of the AC joint <6 months. muscles and splenius), inhibition of muscle trigger points ►► Local or generalised infection. and mobilisation of the AC joint. ►► Severe bleeding disorder and current anticoagulant This joint and muscle work are performed after a phase of therapy (new oral anticoagulants, antivitamin K and evaluation of muscle contractures by shoulder and cervical clopidogrel). muscle palpation and joint amplitudes of the shoulder. The

►► Severe and/or uncontrolled hypertension. evaluation is comparative to the control side. Evaluation of on September 23, 2021 by guest. Protected copyright. ►► Unbalanced diabetes. trigger points corresponds to a pain triggered by a pressure of ►► Live vaccines. 100 g in muscles in preferential area in the muscles described 18 ►► Known allergy to Diprostene, including its excipients by Travell and Simons. The evaluation of muscle corre- (methyl parahydroxybenzoate, propyl parahydroxy- sponds to palpation of muscular fibres, muscular contrac- benzoate and benzyl alcohol). tures and stretch pain. ►► Inflammatory rheumatism (rheumatoid arthritis, Manual therapy does not include cervical manipulations. polymyalgia rheumatica and ankyloses spondylitis). The mobilisations of the AC joints are the same in all patients. ►► Microcrystalline arthritis of the shoulder (gout or The patient sits or is in dorsal decubitus. The mobilisation of calcium pyrophosphate deposition disease). the joint is done by lowering the clavicular, mobilisation of ►► History of surgery or of a shoulder injury requiring a the joint backwards in a sitting position (acromion is brought surgical procedure or arthroscopic intervention. back) and mobilisation with internal rotation of the shoulder ►► Previous injections within the last 6 months. with arm at 90° of abduction. ►► Severe water and/or sodium retention (hyperna- The muscular work will depend on the contractures found tremia), particularly in cases of heart failure, decom- at the initial clinical examination and consist in contrac- pensated liver failure (oedema and ascites) and severe tion and isometric stretching, resting, sliding pressure and renal failure. deep transversal massage on the muscle, that is to say that ►► Immunocompromised or haemodialysis patients. we perform stretching and relaxation on the muscles of

Michaut A, et al. BMJ Open 2020;10:e034439. doi:10.1136/bmjopen-2019-034439 3 Open access BMJ Open: first published as 10.1136/bmjopen-2019-034439 on 10 December 2020. Downloaded from the shoulders, in particular on those which are particularly will be able to carry out this consultation, that is to say the contracted. doctors dedicated to clinical research trained in this study, Ultrasound-guided­ injection of corticosteroids will be there are seven doctors trained). The different examina- performed under strict aseptic conditions after five applica- tions, scores and assessment data will be recorded during tions of Betadine, skin disinfectant, or an equivalent product the different visits according to the schedule listed in table 1. for allergic patients. Injections of 1 mL will be performed Assessment of the main criterion at M3 (VAS activity-­related in accordance with good clinical practice under ultrasound score) will be recorded by a medical evaluator different from guidance by a designated state-registered­ nurse. Dose quan- the physician who performed the manual therapy so as to tity will not be modified, as the product is administered in maintain blinding of the randomisation arm. a single injection. Local injections of corticosteroids can In the control arm, patients will receive a single injec- unbalance diabetes, a psychotic state and severe hyperten- tion of corticosteroids (Diprostene) at D0. They will then sion. They should be administered with caution to patients be seen at a follow-up­ consultation at M1 post-injection­ at a high risk of infection, in particular, those fitted with a by a clinical research nurse and at M3 post-injection­ by prosthetic implant. The risk of a vasomotor reaction and, in a medical assessor. The different examinations, scores particular, of thoracic pain should be taken into consider- and assessment data will be recorded during the different ation in patients with underlying progressive cardiovascular visits according to the schedule listed in table 1. Assess- disease. Care should be taken to not perform intratendinous ment of the main criterion at M3 (VAS activity-related­ injections because of the risk of rupture, nor to use intra- score) will be recorded by a medical evaluator different venous and intramuscular routes. This product cannot be from the physician who administered the injection so as inhaled by nebuliser. to maintain blinding of the randomisation arm. Follow-up­ will be adapted according to the randomisation arm. In the experimental arm, patients will be given between Patient and public involvement one and three sessions of manual therapy at D0, week 1 (W1) There was no patient or public involvement in this study. and week 2 (W2) according to pain progression. They will have a follow-up­ consultation at M1 after the first session with Outcomes a clinical research nurse dedicated to this consultation (there Main assessment criteria is only one nurse who will perform this consultation) and at The main assessment criteria will be the VAS activity-­ M3 after the first session with a doctor (several consultants related score of the patient at M3.

Table 1 Study time frame D0 W12 (M3)

D30 Infiltration or W1 W2 Final http://bmjopen.bmj.com/ Actions Inclusion manipulation *Exp. arm *Exp. arm W4 (M1) assessment Patient information X      Check inclusion/exclusion criteria X      Sign informed consent X      Randomisation X      History X      Clinical examination X X     on September 23, 2021 by guest. Protected copyright. Paraclinical examinations X      AC X-­ray Efficacy and/or safety measurement  X X* X*   Pain VAS procedure DASH questionnaire  X   XX VAS at rest/activity-r­elated pain scores  X   XX VAS at rest/night-­time/activity-­related pain scores  X   XX (mean and maximum) during last 7 days Verbal scale overall assessment     XX Concomitant therapies  X   XX Therapies: Diprostene injection  X     Manipulations  X X X   Adverse events  X X X XX

AC, acromioclavicular; D0, day 0; D30, day 30; DASH, Disabilities of the Arm, Shoulder and Hand; M1, month 1; M3, month 3; VAS, Visual Analogue Scale; W1, week 1; W2, week 2; W4, week 4; W12, week 12.

4 Michaut A, et al. BMJ Open 2020;10:e034439. doi:10.1136/bmjopen-2019-034439 Open access BMJ Open: first published as 10.1136/bmjopen-2019-034439 on 10 December 2020. Downloaded from

Secondary assessment criteria ►► has greatly improved, or ►► The mean and maximum VAS scores of pain at rest ►► is cured? and night-time­ and activity-­related pain during the 7 days preceding the visits at D0, M1 and M3 will be Duration of participation recorded. The patient participation schedule is listed in table 1. The VAS is a self-administered­ test that allows patients Sample size to assess their perceived pain on a rating scale that goes 19 The study is a non-inferiority­ trial on the decrease in from 0 (no pain) to 10 (pain as bad as it could be). activity-­related pain at 3 months as assessed by the differ- A verbal scale is a dynamic criterion that assesses disease ence in the score measured from 3 months to baseline progression in relation to a given reference. It is officially between the groups. In shoulder complaints, a difference recommended for use as a measurement tool in research of 1 in the VAS score (0–10) can be considered clinically projects on arthrosis. Numerous trials have shown it to be 19 significant (Hawker, 2011). In our study, therefore, we effective. decided to set the zone of non-inferiority­ at 1 on the VAS. ►► VAS scores of pain at rest will be recorded during the Alpha and beta risks were set at 2.5% and 20%, respec- visits at D0, M1 and M3 and those of activity-­related tively. We assumed that the common SD between the two pain during the visits at D0 and M1. groups would be 2. On the basis of these different hypoth- Activity-­related pain corresponds to the greatest pain eses, it was calculated that 128 patients would be required felt on movement of the shoulder during abduction, for the study. To guarantee the study’s statistical power, adduction and anteflexion. 5% extra patients will be randomised, making an overall Pain at rest corresponds to the pain felt when the upper total of 136 patients. limb is in a neutral position and relaxed. ►► Scores from the DASH questionnaire, which assesses Recruitment functional disability during daily and leisure activities All patients who were seen in or referred to the Rheuma- and in the workplace, will be recorded at D0, M1 and tology Department of the Vendée Departmental Hospital M3.20 (CHD), France, for AC osteoarthritis and who fulfilled The DASH questionnaire provides a functional score the inclusion criteria of the study were invited to follow for the upper limbs, including the shoulder. It assesses the protocol. The patient inclusion period is 30 months. patient health status in the previous week and has been validated in a French-­language version. It is a 30-­item, self-­ Allocation of the interventions report questionnaire focusing on the difficulty involved in Randomisation: performing various physical activities. The scores range Randomisation will be on a 1:1 ratio basis and performed from 0 to 100 and are calculated on the basis of ((addi- in blocks with Ennov Clinical software: https://nantes-​ ​ tion of answers)−1)×25. lrsy.​hugo-​online.​fr/​EnnovClinical/. Connection will be http://bmjopen.bmj.com/ The score can be validated only if the patient has replied made by login, a password and a study number provided to 90% of the questions (ie, three missing values at most). by the data manager of the Research Unit of the CHD of ►► Patient assessment of the pain felt during the proce- La Roche sur Yon. The investigator will perform rando- dure at the end of the consultation: VAS pain score misation after checking patients’ eligibility to take part after the intervention. in the study and during the visit at D30. The inclusion ►► Verbal scale assessment of overall patient progression number will be assigned automatically at the time of at M1 and M3. randomisation. Confirmation will be sent by email to the

►► Record of the adverse effects and events of the two person who did the randomisation and to all other indi- on September 23, 2021 by guest. Protected copyright. management therapies. viduals concerned. ►► Patient assessment of analgesic consumption during The randomisation list will be created by the statistician the week before the consultation and throughout of the Research Unit of the CHD of La Roche sur Yon. An follow-­up (follow-­up booklet). explanatory guide to the randomisation will be available ►► Assessment of patients’ perception of the procedure online at Ennov Clinical website. before injection or manipulation. Which one do they think will be more painful and which one do they Blinding think will be more effective? Would they recommend The patients will not be blinded to group assignment the procedure they underwent to a relative or friend? because they and the physicians will not be able to distin- ►► During the clinical follow-­up visit at 3 months, the guish between the two treatment methods. The physician patient will be asked the following question: assessor of the main criterion at M3 will be blinded to the In comparison to the beginning of the therapy (D0), do therapy used. you consider that today your shoulder complain: ►► has gotten worse, Data collection ►► is stable or not improved, An electronic Case Report Form (eCRF) will be created ►► shows modest improvement, for each patient. All the information required for the ►► shows mild improvement, protocol will be recorded in the eCRF. This should include

Michaut A, et al. BMJ Open 2020;10:e034439. doi:10.1136/bmjopen-2019-034439 5 Open access BMJ Open: first published as 10.1136/bmjopen-2019-034439 on 10 December 2020. Downloaded from the data that confirm compliance with the protocol and Consumption of analgesics will be recorded throughout all the data needed for statistical analyses. The informa- the study period up to M3. Overall consumption will be tion will indicate any major deviation from the protocol. assessed using a linear regression model. Any missing data will be coded. The person(s) overseeing the completion of the eCRFs will Data monitoring be defined and identified in the table of delegation of respon- Before the beginning of patient recruitment, the health sibilities for each centre (kept in the investigator’s file). professionals involved in the study will attend a training The investigator is responsible for the exactitude, quality session that explains the protocol and how to record the and relevance of all the data entered. In addition, as they are data entered in the eCRF. The eCRF is a secured, inter- entered, the data will be checked immediately by coherence active tool that, in our study, will be managed by the controls. The investigator should check any changes in the hospital’s Promotion Department of the Vendée CHD, eCRF. The changes will be subject to an audit trail. A justifica- La Roche sur Yon. Clinical research physicians and staff tion could be included in the form of a comment. will be in charge of patient screening. The patients will be A database and data entry forms along the lines of the enrolled in the study by a physician in compliance with eCRF will be created to collect the clinical data in accor- the rules of the protocol and data collection. dance with the protocol and existing regulations. The study will be conducted within the framework of the Méthodologie de Référence (Reference Meth- Statistical method odology) MR-001, in conformity with the French Data Statistical analyses will be performed using SAS V.9.4 soft- Protection Law, in application of article 54, paragraph 5 ware. As the study is a non-­inferiority trial, analyses will of law n°78–17 of 6 January 1978 updated (Deliberation be conducted on an intention-­to-­treat basis according to no 2016–262 of 21 July 2016). per-­protocol analysis. The Vendée CHD, La Roche sur Yon, as the promoter Description of the patients is carried out according to of the study, has signed a commitment to comply with the Reference Methodology. the randomisation group on inclusion. The different variables will be presented in their entirety Prejudice and by group. The description will include effectives and A patient can be temporarily withdrawn from the trial by percentages for qualitative variables and the minimum, the physician in charge if there is suspicion of a serious maximum, mean, SD and median for quantitative variables. adverse effect attributable to the product administered during the study. In this event, and in accordance with Analysis of the main criterion French regulations, a specific procedure has been drawn The VAS activity-­related score will be compared in the up and can be consulted in the study protocol. two groups at 3 months. The 95% CI for the difference http://bmjopen.bmj.com/ (manipulation vs injection) between the two VAS scores at Audit M3 will be estimated by a mixed linear model, taking into The Promotion Department of the Clinical Research account the repeated nature of the data. The upper limit Unit of the Vendée CHD performs regular audits of data of the interval of confidence will be the non-­inferiority collection (screening and clinical data). margin defined by 1 point.

Analysis of secondary criteria ETHICS AND DISSEMINATION VAS scores for pain at rest and night-time­ and activity-­ Approval of the ethics committee on September 23, 2021 by guest. Protected copyright. related pain will be recorded at D0, M1 and M3. The The clinical trial will be conducted in accordance with different scores will be compared with a mixed linear the current version of the Declaration of Helsinki and regression model, taking into account the repeated good clinical practice guidelines. The project received nature of the data. approval from the local Ethics Committee for the Protec- Quality of life will be compared on the basis of DASH tion of Patients (Quest II) in Angers, 30 April 2019, with questionnaire scores recorded on D0, M1 and M3. Score the registration number of 2019/22. progression will be assessed using a mixed linear regres- sion model, taking into account the repeated nature of Consent or assent the data. In accordance with existing French regulations, written Patient perception and feelings during the procedure consent to participate in a trial is required from the patient. will be assessed on the basis of a VAS score just after The patient will be asked to give informed consent at the pre-­ the intervention. The scores of the two groups will be enrolment visit at D30 and will provide the signed document compared using Student’s t-­test. to the physician on inclusion. Should the patient decline to The patient’s perception of the disorder will be assessed give consent, the physician undertakes to treat the patient in on a verbal scale at M1 and M3. Score progression will be accordance with existing regulations. A patient can withdraw assessed with a mixed linear regression model, taking into from the study at any time without incurring any liability or account the repeated nature of the data. prejudice as a result, and without any effect on the quality

6 Michaut A, et al. BMJ Open 2020;10:e034439. doi:10.1136/bmjopen-2019-034439 Open access BMJ Open: first published as 10.1136/bmjopen-2019-034439 on 10 December 2020. Downloaded from of care provided. In this event, the patient must inform the of the translations (including but not limited to local regulations, clinical guidelines, physician of his or her decision. terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise. In the event of withdrawal of consent, personal data already collected will be processed using a computer Open access This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-­NC 4.0) license, which unless written opposition is received. permits others to distribute, remix, adapt, build upon this work non-commercially­ , and license their derivative works on different terms, provided the original work is Confidentiality properly cited, appropriate credit is given, any changes made indicated, and the use The study will be conducted in accordance with the guide- is non-­commercial. See: http://​creativecommons.org/​ ​licenses/by-​ ​nc/4.​ ​0/. lines of the French Data Protection Authority and general ORCID iD data protection regulations. All source data will be kept at Grégoire Cormier http://orcid.​ ​org/0000-​ ​0002-8852-​ ​3687 the investigating centre and the coordinating centre for data management. The electronic database will be anonymous and kept for 15 years according to good clinical practice. REFERENCES 1 Chan A-­W, Tetzlaff JM, Gøtzsche PC, et al. SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials. BMJ Conflicts of interest [Internet].. None of the physicians taking part in the study have 2 Juel NG, Natvig B. Shoulder diagnoses in secondary care, a one year conflicts of interest, financial or otherwise, related to cohort. BMC Musculoskelet Disord 2014;15:89. 3 Mall NA, Foley E, Chalmers PN, et al. Degenerative joint disease the conduct of the study. The MSD Laboratories, France, of the acromioclavicular joint: a review. Am J Sports Med which market Diprostene, at no time took part in the 2013;41:2684–92. 4 Saccomanno MF, DE Ieso C, Milano G. Acromioclavicular development of the protocol design and will not inter- joint instability: anatomy, biomechanics and evaluation. Joints vene in any stage of the study (data collection, analysis 2014;2:87–92. and interpretations, and decision to publish). 5 Chaudhury S, Bavan L, Rupani N, et al. Managing acromio-clavicular­ joint pain: a scoping review. Shoulder Elbow 2018;10:4–14. 6 Sabeti-­Aschraf M, Stotter C, Thaler C, et al. Intra-articular­ versus Access to data periarticular acromioclavicular joint injection: a multicenter, Only the coordinating physician and the hospital’s Promo- prospective, randomized, controlled trial. Arthroscopy 2013;29:1903–10. tion Department of the Vendée CHD will have access to 7 Sabeti-­Aschraf M, Ochsner A, Schueller-­Weidekamm C, et al. The the final data for analysis. The physician investigators will infiltration of the ac joint performed by one specialist: ultrasound versus palpation a prospective randomized pilot study. Eur J Radiol by then have signed a no-­access contract. 2010;75:e37–40. 8 Heller GZ, Manuguerra M, Chow R. How to analyze the visual Communication analogue scale: myths, truths and clinical relevance. Scand J Pain The coordinator of the study is committed to communicating 2016;13:67–75. 9 Chelli M, Levy Y, Lavoué V, et al. The "auto-­constant": can we the results of the study to the investigators and participants estimate the constant-­murley score with a self-­administered who ask to be informed. The results will be communicated questionnaire? A pilot study. Orthop Traumatol Surg Res 2019;105:251–6. only after the end of the study, after the last visit of the last 10 HAS. ​EPAULE_​SCORE_​DASH.​pdf. Available: https://www.​s-​f-​t-​s.​ http://bmjopen.bmj.com/ patient or in the event of premature termination of the org/​images/​stories/​documentations/​EPAULE_​SCORE_​DASH.​pdf [Accessed 26 Sept 2018]. trial. The results will be reported to health professionals and 11 Tuton D, Barbe C, Salmon J-H,­ et al. Transcultural validation of the groups of experts via publications and oral communications Oxford shoulder score for the French-­speaking population. Orthop or posters at medical congresses. Traumatol Surg Res 2016;102:555–8. 12 Barwood SA, French JA, Watson LA, et al. The specific AC Practical arrangements concerning rules for publica- score (sacs): a new and validated method of assessment of tion will be established in agreement with the physician isolated acromioclavicular joint pathology. J Shoulder Elbow Surg 2018;27:2214–23. investigators and other participants in the study. 13 Park KD, Kim TK, Lee J, et al. Palpation versus ultrasound-­guided

acromioclavicular joint intra-­articular corticosteroid injections: on September 23, 2021 by guest. Protected copyright. Acknowledgements Jeffrey Watts for translation. a retrospective comparative clinical study. Pain Physician 2015;18:333–41. Contributors AM, GC, LA and LP wrote the manuscript and took part in the study 14 Rhon DI, Boyles RB, Cleland JA. One-­year outcome of subacromial design. LP wrote the statistical analysis plan and estimated the sample size. AM, corticosteroid injection compared with manual physical therapy for GC, LA and LP obtained funding for the study. All the authors contributed to data the management of the unilateral shoulder impingement syndrome: a collection, made a critical reading of the manuscript and read and approved the pragmatic randomized trial. Ann Intern Med 2014;161:161–9. final version. 15 Harris KD, Deyle GD, Gill NW, et al. Manual physical therapy for injection-­confirmed nonacute acromioclavicular joint pain. J Orthop Funding This study was supported by a grant from CHD Vendée in response to an Sports Phys Ther 2012;42:66–80. internal call for bids. 16 Winters JC, Sobel JS, Groenier KH, et al. Comparison of physiotherapy, manipulation, and corticosteroid injection for treating Competing interests None declared. shoulder complaints in general practice: randomised, single blind Patient consent for publication Not required. study. BMJ 1997;314:1320–5. 17 Peek AL, Miller C, Heneghan NR. Thoracic manual therapy in the Provenance and peer review Not commissioned; externally peer reviewed. management of non-­specific shoulder pain: a systematic eview.r J Supplemental material This content has been supplied by the author(s). It has Man Manip Ther 2015;23:176–87. 18 Shah JP, Thaker N, Heimur J, et al. Myofascial trigger points then and not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been now: a historical and scientific perspective. Pm R 2015;7:746–61. peer-reviewed.­ Any opinions or recommendations discussed are solely those 19 Haefeli M, Elfering A. Pain assessment. Eur Spine J 2006;15:S17–24. of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and 20 HAS. ​EPAULE_​SCORE_​DASH.​pdf+. Available: https://www.​s-​f-​t-​s.​ responsibility arising from any reliance placed on the content. Where the content org/​images/​stories/​documentations/​EPAULE_​SCORE_​DASH.​pdf includes any translated material, BMJ does not warrant the accuracy and reliability [Accessed 8 Jan 2020].

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